What clinical trials currently test transcranial magnetic stimulation for tinnitus and what outcomes do they report?
Executive summary
Repetitive transcranial magnetic stimulation (rTMS) has been the subject of numerous clinical trials for chronic tinnitus over the past two decades, but results are inconsistent: some randomized controlled trials and meta-analyses report modest short-term reductions in tinnitus loudness or handicap, while larger and more recent trials show little or no benefit and wide heterogeneity in outcomes [1] [2] [3]. Contemporary investigational work has shifted toward multilocus and high-frequency protocols and feasibility studies, yet reviewers and cochranes conclude that definitive large-scale, multisite randomized trials with standardized protocols are still lacking [4] [5] [6].
1. The randomized trials that set the baseline: mixed signals from RCTs
Early and mid-era randomized clinical trials — including a notable JAMA Otolaryngology trial led by Folmer and colleagues and other sham-controlled RCTs — tested low-frequency and other rTMS regimens against placebo with follow-up out to six months, producing mixed results: some trials reported statistically significant responder rates or reduced loudness at certain time points, while others found no difference from sham [7] [8] [1]. Systematic reviews pooling small trials found some pooled reductions in loudness when limited sets of studies were combined, but confidence intervals and methodological heterogeneity weakened the strength of inference [2] [3].
2. What meta-analyses and reviews conclude: signals but not consensus
Multiple systematic reviews and meta-analyses through 2020 and earlier concluded that rTMS can yield clinically meaningful improvements in some trials, yet overall evidence is inconsistent and highly variable across studies; reviewers repeatedly call for larger, better-powered, standardized trials because small sample sizes and divergent stimulation parameters produce wide outcome heterogeneity [1] [3] [2]. The Cochrane review likewise identified only a handful of eligible trials with a total of a few hundred patients and concluded that while one study showed a partial THI improvement, evidence remains insufficient to recommend routine use [6].
3. Contemporary trial designs: multilocus, high-frequency, feasibility and observational studies
More recent investigations have examined multilocus sequential rTMS targeting both prefrontal and auditory cortical regions and high-frequency stimulation regimens in feasibility or observational settings; an institutional observational series at UCLA enrolled 40 patients treated with sequential multilocus protocols and reported clinically meaningful improvements in many participants, with those who had comorbid major depressive disorder sometimes requiring extended courses for maximal benefit [9] [10]. A 2024 feasibility study of high-frequency rTMS in eleven adults focused on safety and preliminary efficacy, reflecting a shift toward small, mechanism-oriented trials rather than large definitive RCTs [11].
4. Safety profile and adverse events reported across trials
Across randomized and observational studies included in systematic reviews, no serious adverse effects were commonly reported and rTMS has been portrayed as generally safe in tinnitus populations, though studies emphasize monitoring and standardized reporting of side effects going forward [2] [3]. Trial registries for earlier RCTs (for example NCT01104207) document standard safety monitoring procedures even where public results summaries are limited [12] [8].
5. Why trials disagree: targets, parameters, populations and methodology
A recurrent theme in the literature is technical and clinical heterogeneity — differing stimulation frequencies (low vs. high), scalp targets (left auditory cortex, bilateral, or multilocus including dorsolateral prefrontal cortex), session number, and patient characteristics such as age, tinnitus chronicity, hearing loss, and comorbid depression — all likely contribute to divergent outcomes between otherwise similar trials, and authors urge standardized parameter reporting and multicenter replication [4] [5] [1].
6. The current state of evidence and the research gap to be filled
The evidence base shows promising, reproducible positive findings in some small trials and observational series but lacks the large, multicenter randomized controlled trials with standardized protocols and long-term follow-up necessary to determine which rTMS approaches — if any — reliably improve tinnitus across defined patient subgroups; leading reviews and the Cochrane Collaboration explicitly call for such trials to resolve uncertainties [5] [6] [3]. Clinical trial registries list past and ongoing registrations but published definitive, consistent positive results that would change clinical practice are not yet available in the assembled reporting [12] [13] [8].